The Immune Function Studies Core (Core C) is designed to support the proposed studies of yc Foamy Virus gene therapy for SCID-Xl that will utilize in vitro testing in cell lines as well as in vivo testing using pre- clinical animal models. The Core will support all three projects (1, 2, and 3) of this Program Project Grant and is focused primarily on evaluation of functional immune recovery after gene therapy in this severe immunodeficiency disorder. The Core will perform multi-parameter flow cytometry analyses of human, mouse, and canine cells to measure viral marking and immune reconstitution after yc FV gene therapy. In addition. Core C will evaluate restoration of specific functional deficits (for example restoration of lL-2 signaling) in yc FV treated cells and will work with the SCRl Immunology Diagnostic Laboratory (IDL) to analyze functional immune responses to neoantigen (bacteriophage OX174) vaccination in treated dogs. Flow cytometry and gene sequencing will be performed by the Core to rapidly identify affected SCID-Xl dogs shortly after birth. Core C personnel will directly assist project investigators in the analysis and interpretation of data generated by the Core. Data from these analyses will be used to evaluate which yc FV vector is most efficacious and which conditioning regimen facilitates the most complete immune recovery.